Killing The Messenger: Exploring Novel Triggers For Messenger Rna Decay In Eukaryotes

Simple item page
dc.contributor.advisorBrian D. Gregory
dc.contributor.authorVandivier, Lee Elliott
dc.date2023-05-17T19:42:17.000
dc.date.accessioned2023-05-22T17:12:20Z
dc.date.available2001-01-01T00:00:00Z
dc.date.copyright2018-02-23T20:17:00-08:00
dc.date.issued2017-01-01
dc.date.submitted2018-02-23T12:42:06-08:00
dc.description.abstractThe lifecycle of messenger RNAs is regulated by multiple layers beyond their primary sequence. In addition to carrying the information for protein synthesis, mRNAs are decorated with RNA binding proteins, marked with covalent chemical modifications, and fold into intricate secondary structures. However, the full set of information encoded by these “epitranscriptomic” layers is only partially understood, and is often only characterized for select transcripts. Thus, it is crucial to develop and apply transcriptome-wide analytical tools to probe the location and functional relevance of epitranscriptome features. In this dissertation, I focus on applying such methods toward better understanding determinants of mRNA stability, through using 1) High Throughput Annotation of Modified Nucleotides, 2) nuclease-mediated probing of RNA secondary structure, and 3) detection of partial mRNA degradation from RNA sequencing. I observe that chemical modifications tend to mark uncapped and small RNA fragments derived from mRNAs in plants and humans, suggesting a link between modifications and mRNA stability. I then show this link is direct through showing differential stability at Arabidopsis transcripts that change modification status during long-term salt stress. By probing secondary structure, I show a link between structure, smRNA production, and co-translational RNA decay. Finally, I develop a new in silico method to detect partial RNA degradation in mouse oocytes, and identify sequence elements that appear to block complete exonucleolytic transcript cleavage during meiosis. I then identify putative RNA binding proteins that might mediate this partial decay. In summary, I apply transcriptome-wide sequencing-based methods to survey the effects of covalent modifications, secondary structure, and RNA binding proteins on mRNA stability.
dc.description.degreeDoctor of Philosophy (PhD)
dc.format.extent228 p.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/29559
dc.languageen
dc.legacy.articleid4407
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=4407&context=edissertations&unstamped=1
dc.provenanceReceived from ProQuest
dc.rightsLee Elliott Vandivier
dc.source.issue2621
dc.source.journalPublicly Accessible Penn Dissertations
dc.source.statuspublished
dc.subject.otherBioinformatics
dc.subject.otherBiology
dc.subject.otherGenetics
dc.titleKilling The Messenger: Exploring Novel Triggers For Messenger Rna Decay In Eukaryotes
dc.typeDissertation/Thesis
digcom.contributor.authorisAuthorOfPublication|email:evlee@mail.med.upenn.edu|institution:University of Pennsylvania|Vandivier, Lee Elliott
digcom.date.embargo2001-01-01T00:00:00-08:00
digcom.identifieredissertations/2621
digcom.identifier.contextkey11637281
digcom.identifier.submissionpathedissertations/2621
digcom.typedissertation
dspace.entity.typePublication
relation.isAuthorOfPublicationeedad8f5-6658-45cc-9ba6-87186c98a5a2
relation.isAuthorOfPublication.latestForDiscoveryeedad8f5-6658-45cc-9ba6-87186c98a5a2
upenn.graduate.groupCell & Molecular Biology
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Vandivier_upenngdas_0175C_12932.pdf
Size:
7.22 MB
Format:
Adobe Portable Document Format
Download
Collection
Dissertations and Theses